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Juvenile primary Sjögren syndrome (pSS) with renal involvement is extremely rare, reported approximately in 50 children, predominantly girls. Here, we present the first reported case of a male child with juvenile pSS with ocular surface disease (previously keratoconjunctivitis sicca), submandibular salivary gland involvement, and tubulointerstitial nephritis. First, two symptoms were clinically apparent at presentation. We illustrate here that kidney involvement in pSS should be actively looked for, as juvenile pSS may be associated with asymptomatic renal involvement. Immunophenotyping of peripheral blood cells using multicolor flow cytometry revealed at the time of diagnosis changes in both adaptive (T memory cells and B memory cells), and innate immunity (an increased activation of natural killer cells, as well as monocytes and neutrophils, and an increased representation of intermediate monocytes). Our case report points to the importance of kidney examination, early diagnosis and therapy in juvenile pSS, as well as highlights international collaboration to obtain more data for this rare disease.

BackgroundFactor H-related protein 5 (FHR-5) is a member of the complement Factor H protein family. Due to the homology to Factor H, the main complement regulator of the alternative pathway, it may also be implicated in the pathomechanism of kidney diseases where Factor H and alternative pathway dysregulation play a role. Here, we report the first observational study on CFHR5 variations along with serum FHR-5 levels in immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) and C3 glomerulopathy (C3G) patients together with the clinical, genetic, complement, and follow-up data.MethodsA total of 120 patients with a histologically proven diagnosis of IC-MPGN/C3G were enrolled in the study. FHR-5 serum levels were measured in ELISA, the CFHR5 gene was analyzed by Sanger sequencing, and selected variants were studied as recombinant proteins in ELISA and surface plasmon resonance (SPR).ResultsEight exonic CFHR5 variations in 14 patients (12.6%) were observed. Serum FHR-5 levels were lower in patients compared to controls. Low serum FHR-5 concentration at presentation associated with better renal survival during the follow-up period; furthermore, it showed clear association with signs of complement overactivation and clinically meaningful clusters.ConclusionsOur observations raise the possibility that the FHR-5 protein plays a fine-tuning role in the pathogenesis of IC-MPGN/C3G.

Antenatal hydronephrosis, dilatation of the upper urinary tract (UUTD), is a common finding on prenatal ultrasound. One of the most common causes is ureteropelvic junction (UPJ) obstruction. Although such prenatally diagnosed UUTD resolves spontaneously in most newborns, further examination of these children is advocated to prevent possible irreversible kidney damage, and ultrasound is mainly used for this. If the dilatation persists or becomes symptomatic, it is necessary to proceed to other relatively demanding and invasive diagnostic examinations for these small patients, where the question of the right timing of indications for possible surgical solutions is still unclear. For this reason, various biomarkers have been investigated in a number of clinical trials as potential mini-invasive diagnostic tools for determining when upper urinary tract dilatation in such children poses a threat to the developing kidneys and they should be operated on, and vice versa, when to proceed conservatively. The aim of this article is to review the findings on and current issues with the use of biomarkers in the diagnosis and treatment of UPJ obstruction in children.

Patients on long-term home parenteral nutrition (HPN) occasionally develop glomerulonephritis due to chronic central venous catheter (CVC)-related infection. Most previously reported cases were membranoproliferative glomerulonephritis (MPGN). This is a case report of a 16-year-old girl receiving HPN for short bowel syndrome. After 11 years on HPN, she developed acute kidney injury with macroscopic hematuria, nephrotic-range proteinuria, and a reduced glomerular filtration rate (GFR). Initially, MPGN associated with chronic bacteremia was suspected with the assumption that the condition would be treated with antibiotics and CVC replacement. However, her kidney biopsy revealed antineutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis (AAG). This was consistent with the fact that the patient tested positive for proteinase 3-ANCA. Immunosuppressive therapy with methylprednisolone pulses (followed by oral prednisone) and rituximab led to remission. Her GFR and protein excretion returned to normal. Chronic bacteremia as a complication of long-term HPN may cause various types of glomerulonephritis including, rarely, AAG requiring immunosuppressive therapy.

Aim: To assess of the role of renal ultrasonography (US) and DMSA renal scintigraphy in the prediction of irreversible histological lesions of the upper pole in duplex system. Methods: A prospective cohort study based on data collected between 2005 and 2012 at our institution. The cohort consisted of 23 patients with ureteroceles and 28 patients with ectopic ureters who underwent upper pole nephrectomy. Preoperative recordings from ultrasound and nuclear renal scans were compared with the histological findings. Histological irreversible lesions were defined as the presence of dysplasia and/or severe chronic interstitial nephritis (CIN) in ≥ 90% of the specimen. ROC (Receiver Operating Characteristic) curves were used to investigate thresholds in order to identify irreversible lesions using various differential functions. The histology was correlated with the results of imaging. Results: Pathological findings were found in all histological samples. Histological lesions were irreversible in 20/23 patients (87.0%) with ureteroceles and in 14/28 patients (50.0%) with ectopic ureters. The model is able to predict irreversible lesions if an upper pole differential function is ≤ 3% in patients with ureteroceles, and ≤ 2% in the presence of ectopic ureters. Weak association between parenchymal thinning on ultrasonography and irreversible lesions was found in patients with ectopic ureters. Conclusion: DMSA renal scintigraphy provides a useful tool for the prediction of irreversible lesions in the upper pole. Low differential function (≤ 3% and ≤ 2%, respectively) indicates irreversible lesions, favoring heminephrectomy. Higher differential function indicates greater remaining biological potential of the parenchyma, favoring reconstruction of the upper pole.

Abstract Background Acquired or genetic abnormalities of the complement alternative pathway are the primary cause of C3glomerulopathy(C3G) but may occur in immune-complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) as well. Less is known about the presence and role of C4nephritic factor(C4NeF) which may stabilize the classical pathway C3-convertase. Our aim was to examine the presence of C4NeF and its connection with clinical features and with other pathogenic factors. Results One hunfe IC-MPGN/C3G patients were enrolled in the study. C4NeF activity was determined by hemolytic assay utilizing sensitized sheep erythrocytes. Seventeen patients were positive for C4NeF with lower prevalence of renal impairment and lower C4d level, and higher C3 nephritic factor (C3NeF) prevalence at time of diagnosis compared to C4NeF negative patients. Patients positive for both C3NeF and C4NeF had the lowest C3 levels and highest terminal pathway activation. End-stage renal disease did not develop in any of the C4NeF positive patients during follow-up period. Positivity to other complement autoantibodies (anti-C1q, anti-C3) was also linked to the presence of nephritic factors. Unsupervised, data-driven cluster analysis identified a group of patients with high prevalence of multiple complement autoantibodies, including C4NeF. Conclusions In conclusion, C4NeF may be a possible cause of complement dysregulation in approximately 10–15% of IC-MPGN/C3G patients.